Laboratorio de Células Neurales Troncales Humanas, Coordinación para la Innovación y Aplicación de la Ciencia y la Tecnología-Facultad de Medicina, Universidad Autónoma de San Luis Potosí, San Luis Potosí, México.
Sección de Microscopia de Alta Resolución, Centro de Investigación en Ciencias de la Salud y Biomedicina, Universidad Autónoma de San Luis Potosí, San Luis Potosí, México.
PLoS One. 2023 Mar 29;18(3):e0283429. doi: 10.1371/journal.pone.0283429. eCollection 2023.
Zika virus (ZIKV) was first isolated in 1947. From its isolation until 2007, symptoms of ZIKV-caused disease were limited (e.g., fever, hives, and headache); however, during the epidemic in Brazil in 2014, ZIKV infection caused Guillain-Barré syndrome in adults and microcephaly in fetuses and infants of women infected during pregnancy. The neurovirulence of ZIKV has been studied using neural progenitor cells (NPCs), brain organoids, neurons, and astrocytes. NPCs and astrocytes appear to be the most susceptible cells of the Central Nervous System to ZIKV infection. In this work, we aimed to develop a culture of astrocytes derived from a human NPC cell line. We analyze how ZIKV affects human astrocytes and demonstrate that 1) ZIKV infection reduces cell viability, increases the production of Reactive Oxygen Species (ROS), and results in high viral titers; 2) there are changes in the expression of genes that facilitate the entry of the virus into the cells; 3) there are changes in the expression of genes involved in the homeostasis of the glutamatergic system; and 4) there are ultrastructural changes in mitochondria and lipid droplets associated with production of virions. Our findings reveal new evidence of how ZIKV compromises astrocytic functionality, which may help understand the pathophysiology of ZIKV-associated congenital disease.
寨卡病毒（ZIKV）于 1947 年首次被分离出来。从被分离出来到 2007 年，寨卡病毒引起的疾病症状有限（例如发热、荨麻疹和头痛）；然而，在 2014 年巴西的流行中，寨卡病毒感染导致成年人出现格林-巴利综合征，孕妇感染后胎儿和婴儿出现小头畸形。神经毒力的寨卡病毒已使用神经祖细胞（NPCs）、脑类器官、神经元和星形胶质细胞进行了研究。NPCs 和星形胶质细胞似乎是寨卡病毒感染的中枢神经系统中最易受影响的细胞。在这项工作中，我们旨在开发源自人 NPC 细胞系的星形胶质细胞培养。我们分析了寨卡病毒如何影响人星形胶质细胞，并证明 1）寨卡病毒感染会降低细胞活力，增加活性氧物质（ROS）的产生，并导致高病毒滴度；2）促进病毒进入细胞的基因表达发生变化；3）参与谷氨酸能系统稳态的基因表达发生变化；以及 4）与病毒粒子产生相关的线粒体和脂滴的超微结构发生变化。我们的研究结果揭示了寨卡病毒损害星形胶质细胞功能的新证据，这可能有助于理解寨卡病毒相关先天性疾病的病理生理学。
